Nuclear factor of activated T cells (hereinafter singly referred to as “NFAT”) was discovered as a factor that activates transcription of interleukin-2 (IL-2), which is important for the activation of T cells, and it has been reported that the transcription activity of NFAT is regulated by a serine/threonin phosphatase, calcineurin, which is a target of immunosuppressants such as cyclosporin A (hereinafter simply referred to as “CsA”) and tacrolimus (hereinafter simply referred to as “FK506”) (see FIG. 2). That is, CsA and FK506 suppress T cell activation by inhibiting the NFAT signal. CsA and FK506 have been approved not only as a transplant immunosuppressant but also as a therapeutic drug for rheumatoid arthritis, psoriasis, and atopic dermatitis, which are known to be involved in the immune system. The system in which when such an NFAT binds to an NFAT binds to an NFAT-binding sequence (“NFAT site” in FIG. 2), transcription of genes downstream of NFAT-binding sequence is promoted, is referred to as “NFAT signal.”
On the other hand, it has been reported that a hair-growing (including hair regrowth) effect could be attained through inhibition of NFAT signal (Non-Patent Document 1). It has been also reported that a CsA derivative which inhibits NFAT signal may also serve as a hair growing agent (Patent Documents 1, 2).
Furthermore, NFAT not only has an action on hair growth or an action on the immune system, but is also expressed in many organs and has been recognized as “multifunctional” transcription factor that fulfills critical roles, for example, formation of muscular tissues due to the regulation of heart muscle and skeletal muscle differentiation, formation of a neuro-network in the brain, bone metabolism due to the regulation of osteoblastic differentiation, and the like.
The role of NFAT signal that affects the living body is as discussed above, but it has been reported that when the NFAT signal is inhibited, an immunosuppressive action (Non-Patent Document 2), treatment of psoriasis (Non-Patent Document 3), treatment of atopic dermatitis (Non-Patent Document 4), suppression of (cardiac) muscle hypertrophy (Non-Patent Document 5), a potential of an anti-rheumatic drug (Non-Patent Document 6), a suppressive action on osteoclast differentiation (Non-Patent Document 7), and the like can be expected. Furthermore, since NFAT is mediated by a pathway to produce immune cytokine IL-2, as described above, an NFAT signal inhibitor is useful for the treatment or prevention of diseases that are considered to involve immune cytokine, including autoimmune disease.
Examples of such target diseases include various cancers, various leukemia, various hepatitis, various infections, systemic lupus erythematosus, inflammatory bowel diseases (ulcerative colitis, Crohn's disease), multiple sclerosis, insulin-dependent diabetes, peptic ulcer, septic shock, tuberculosis, infertility, arteriosclerosis, Behcet's disease, asthma, nephritis, acute bacterial meningitis, acute myocardial infarction, acute pancreatitis, acute viral encephalitis, adult acute respiratory distress syndrome, bacterial pneumonia, chronic pancreatitis, peripheral vascular diseases, sepsis, interstitial liver diseases, situational ileitis, and multiple sclerosis. Therefore, when a novel NFAT signal inhibitor is identified, uses thereof as an immunosuppressant, a therapeutic agent for psoriasis, a therapeutic agent for atopic dermatitis, a suppressant for (cardiac) muscle hypertrophy, an anti-rheumatic drug, a therapeutic agent for bone metabolic diseases, and novel medicinal uses such as listed above are expected. Furthermore, when a novel NFAT signal inhibitor is identified, uses thereof as a quasi-drug such as a hair-growing agent or a hair regrowth promoting agent, and cosmetic uses are expected.
Meanwhile, there has been reported that extracts of plants belonging to the genus Angelica are'recognized to have a hair-growing, hair regrowth, or hair-nourishing effect (Patent Documents 3 to 6). Specifically, Patent Document 3 discloses a hair-nourishing/hair-growing agent containing a Dong Quai (Angelica sinensis) extract. Patent Document 4 discloses a hair-nourishing agent containing an essential oil of Angelica glauca. Patent Document 5 discloses a hair regrowth and hair growth promoting material containing an extract of Bai Zhi (Angelica dahurica Benth. Et Hook). Patent Document 6 discloses a hair beautifying material such as a hair-growing and hair-nourishing agent containing an extract of Ashitaba (Angelica Keiskei Koidz).
However, there has been no report that suggests the relationship between NFAT signal and the aforementioned plants belonging to the genus Angelica. Among plants belonging to the genus Angelica, American angelica (Angelica atropurpurea) has never been known to have a hair growth, a hair regrowth action, or the like, and use of American angelica (i.e., application to the skin) has never been reported.